SH 159's southern terminus is a continuation as New Mexico State Road 522 (NM 522) at the New Mexico state line, and the northern terminus is at U.S. Route 160 (US 160) near Fort Garland.

SH 159 starts in the south at the New Mexico state line where the road becomes NM 522 which heads south towards Taos, NM.

From the state line the road heads north to meet US 160 at its north end just outside Fort Garland.

There is only one town along the route, San Luis, which is at the road's midpoint.

Media related to Colorado State Highway 159 at Wikimedia Commons